Evidence map›Paper›PMID 38820342›Full record

ArticlePloS one2024

Polygenic risk score for acute rejection based on donor-recipient non-HLA genotype mismatch.

Rui Cao, David P Schladt, Casey Dorr, Arthur J Matas, William S Oetting, Pamala A Jacobson, Ajay Israni, Jinbo Chen, Weihua Guan

2 registry-linked trialsAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PloS one, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00270712 completednot on this map

Study of Long-term Deterioration of Kidney Allograft Function (DeKAF)

TypeobservationalSponsorUniversity of MinnesotaRan2005 to 2018Enrolled3,175ConditionsKidney Transplant
NCT01714440 completednot on this map

Genomics of Kidney Transplantation

TypeobservationalSponsorNational Institute of Allergy and Infectious Diseases (NIAID)Ran2012 to 2017Enrolled1,552ConditionsKidneyTransplant Recipients, Simultaneous Kidney/Pancreas Recipients, Kidney Transplant Donor
3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Genome-wide donor-recipient non-HLA mismatch and graft loss.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025
    Pooled it
  2. Article
  3. Review
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Rui CaoDivision of Biostatistics and Health Data Science, School of Public Health, University of Minnesota, Minneapolis, Minnesota, United States of America.ORCID 0009-0005-5157-2396
David P SchladtHennepin Healthcare Research Institute, Minneapolis, Minnesota, United States of America.ORCID 0000-0002-3793-5745
Casey DorrHennepin Healthcare Research Institute, Minneapolis, Minnesota, United States of America.
Arthur J MatasDepartment of Surgery, University of Minnesota Medical School, Minneapolis, Minnesota, United States of America.
William S OettingDepartment of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, United States of America.
Pamala A JacobsonDepartment of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, United States of America.
Ajay IsraniHennepin Healthcare Research Institute, Minneapolis, Minnesota, United States of America.
Jinbo ChenDepartment of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Weihua GuanDivision of Biostatistics and Health Data Science, School of Public Health, University of Minnesota, Minneapolis, Minnesota, United States of America.ORCID 0000-0002-0956-9821

Funding

Pharmacogenomics of Immune Suppressants in Kidney TransplantationU19AI070119 · NIAID · UNIVERSITY OF MINNESOTA · PI MATAS, ARTHUR J · 2006 to 2016
$17.1M
Long-term Deterioration of Kidney Allograft FunctionU01AI058013 · NIAID · UNIVERSITY OF MINNESOTA TWIN CITIES · PI MATAS, ARTHUR J · 2005 to 2010
$10.2M
NIAID NIH HHS U01 AI058013NIAID NIH HHS U19 AI070119
6 · The paper itself

Abstract

backgroundAcute rejection (AR) after kidney transplantation is an important allograft complication. To reduce the risk of post-transplant AR, determination of kidney transplant donor-recipient mismatching focuses on blood type and human leukocyte antigens (HLA), while it remains unclear whether non-HLA genetic mismatching is related to post-transplant complications.

methodsWe carried out a genome-wide scan (HLA and non-HLA regions) on AR with a large kidney transplant cohort of 784 living donor-recipient pairs of European ancestry. An AR polygenic risk score (PRS) was constructed with the non-HLA single nucleotide polymorphisms (SNPs) filtered by independence (r2 < 0.2) and P-value (< 1×10-3) criteria. The PRS was validated in an independent cohort of 352 living donor-recipient pairs.

resultsBy the genome-wide scan, we identified one significant SNP rs6749137 with HR = 2.49 and P-value = 2.15×10-8. 1,307 non-HLA PRS SNPs passed the clumping plus thresholding and the PRS exhibited significant association with the AR in the validation cohort (HR = 1.54, 95% CI = (1.07, 2.22), p = 0.019). Further pathway analysis attributed the PRS genes into 13 categories, and the over-representation test identified 42 significant biological processes, the most significant of which is the cell morphogenesis (GO:0000902), with 4.08 fold of the percentage from homo species reference and FDR-adjusted P-value = 8.6×10-4.

conclusionsOur results show the importance of donor-recipient mismatching in non-HLA regions. Additional work will be needed to understand the role of SNPs included in the PRS and to further improve donor-recipient genetic matching algorithms. Trial registry: Deterioration of Kidney Allograft Function Genomics (NCT00270712) and Genomics of Kidney Transplantation (NCT01714440) are registered on ClinicalTrials.gov.

Indexed as

Genome-Wide Association StudyGenotypeGraft RejectionKidney TransplantationPolymorphism, Single NucleotideAdultCohort StudiesFemaleGenetic Risk ScoreHLA AntigensHumansLiving DonorsMaleMiddle AgedMultifactorial InheritanceRisk FactorsHLA Antigens

Identifiers

PMID38820342
PMCPMC11142483

What Socratic holds

Textmetadata
LicenceCC BY
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.